Ferroptosis is a recently characterized form of regulated cell death. Which best describes its mechanism?

• A Caspase-1 mediated cleavage of gasdermin D in the setting of NLRP3 inflammasome activation
• B RIPK3-MLKL signaling axis causing plasma membrane disruption analogous to necroptosis
• C GPX4-dependent reduction of phospholipid hydroperoxides is impaired, allowing iron-catalyzed lipid peroxidation to propagate membrane destruction ✓
• D BAX/BAK pore-mediated cytochrome c release from mitochondria triggering apoptosome

Explanation

Ferroptosis is driven by accumulation of oxidized phospholipids (lipid peroxidation products) in cell membranes. Glutathione peroxidase 4 (GPX4) normally reduces toxic phospholipid hydroperoxides using glutathione as reductant. When GPX4 is inhibited (e.g., by erastin blocking cystine import → depleted GSH, or by direct GPX4 inhibitors like RSL3), iron-catalyzed Fenton reactions oxidize polyunsaturated fatty acid-containing phospholipids causing membrane rupture. This is distinct from pyroptosis (gasdermin D), necroptosis (MLKL), and intrinsic apoptosis (BAX/BAK).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.